Abstract
MicroRNA expression profiling in human liver progenitor cells following hepatocytic differentiation identified miR-122 and miR-194 as the microRNAs most strongly upregulated during hepatocytic differentiation of progenitor cells. MiR-194 was also highly upregulated following hepatocytic differentiation of human embryonic stem cells (hESCs). Overexpression of miR-194 in progenitor cells accelerated their differentiation into hepatocytes, as measured by morphological features such as canaliculi and expression of hepatocytic markers. Overexpression of miR-194 in hESCs induced their spontaneous differentiation, a phenotype accompanied with accelerated loss of the pluripotent factors OCT4 and NANOG and decrease in mesoderm marker HAND1 expression. We then identified YAP1 as a direct target of miR-194. Inhibition of YAP1 strongly induced hepatocytic differentiation of progenitor cells and YAP1 overexpression reversed the miR-194-induced hepatocytic differentiation of progenitor cells. In conclusion, we identified miR-194 as a potent inducer of hepatocytic differentiation of progenitor cells and further identified YAP1 as a mediator of miR-194's effects on hepatocytic differentiation and liver progenitor cell fate.
Original language | English (US) |
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Pages (from-to) | 1284-1296 |
Number of pages | 13 |
Journal | STEM CELLS |
Volume | 34 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2016 |
Keywords
- Differentiation
- Hepatocytes
- Progenitor cells
- YAP1
- miR-194
ASJC Scopus subject areas
- Molecular Medicine
- Developmental Biology
- Cell Biology
MD Anderson CCSG core facilities
- Functional Genomics Core